Risk for Opioid Abuse and Misuse in Adolescence Abstract Current rates of prescription opioid misuse are rising to epidemic levels among adults. These rates may be even higher among adolescents, who have elevated levels of substance exploration and misuse during this precise developmental period. Adolescents who are exposed to opioids via legitimate prescriptions are at increased risk for misuse after high school. However, there is a substantial gap in our knowledge of what factors might contribute to the development of misuse and related poor outcomes in these high-risk youth. Identifying factors that convey risk for increasing opioid use and problematic use would inform adolescent models of opioid abuse and inform the development of preventive interventions to modify risk in the medical setting. The pediatric medical setting, where adolescents are exposed to opioids via legitimate prescription is a unique point of entry into opioid use, and a key setting in which to examine adolescent outcomes. The proposed study will utilize a developmental model of the impact of opioid exposure by legitimate prescription during late adolescence, with consideration for pain and psychological characteristics of the individual within the family and peer context. Predictors and mechanisms of increasing opioid use and problematic use will be examined over a 2 year time period during late adolescence. The central hypothesis is that adolescent pain characteristics will influence opioid use and problems over time, and that opioid availability will mediate this association. Pain medication specific parent factors will also be examined, including parental chronic pain and opioid prescriptions, attitudes about pain medications, and pain catastrophizing. Longitudinal models of opioid use and opioid problems will be tested in a sample of 14-18 year olds receiving opioid prescriptions for non- cancer pain in outpatient medical settings (n= 500 adolescents and a parent will be enrolled). These adolescents will be assessed every 6 months for 2 years, and will report on pain characteristics, opioid and other substance use and problems, peer factors, as well as pain catastrophizing and other pain-related psychological factors. Objective data on dispensed opioid medications will be obtained from prescription drug monitoring databases. Daily associations between adolescent pain, pain catastrophizing, and opioid use will also be examined. Determining mechanisms and moderators of risk during this developmental transition will provide critical information for the design of interventions aimed at reducing opioid use disorders in at-risk youth.